The present invention generally relates to the production of radionuclides suitable for use in diagnostic and therapeutic radiopharmaceuticals, and specifically, to a system and method for producing radionuclides from a solid target material using a low or medium energy charged-particle accelerator. The invention particularly relates, in a preferred embodiment, to a system and method for producing .sup.64 Cu and other intermediate half-lived positron-emitting radionuclides using a biomedical cyclotron capable of generating protons at energies ranging from about 5 MeV to about 25 MeV.
Low or medium energy charged-particle accelerators such as biomedical cyclotrons have been used to produce short-lived radionuclides such as .sup.15 O (t.sub.1/2 =2 minutes), .sup.13 N (t.sub.1/2 =9.96 minutes), .sup.11 C (t.sub.1/2 =20.4 minutes) and .sup.18 F (t.sub.1/2 =110 minutes) from gaseous target sources. The on-site production of these radionuclides at medical research and/or treatment centers facilitate their immediate use in diagnostic and therapeutic applications. However, other radionuclides which have become increasingly important for such applications are not currently available using an on-site accelerator in commercially significant yields and at specific activities suitable for diagnostic and therapeutic uses. For example, .sup.4 Cu is an intermediate half-lived positron-emitting radionuclide (t.sub.1/2 =12.7 hours) which is a useful radiotracer for positron emission tomography (PET) as well as a promising radiotherapy agent for the treatment of cancer. (Anderson et al., 1992; Anderson et al., 1993; Connett et al., 1993; Philpott et al., 1993; Anderson et al., 1994; Anderson et al., 1995a; Anderson, et al., 1995b). However, .sup.64 Cu is presently produced in clinically significant yields and specific activities only through fast neutron reactions using a nuclear reactor. (Herr and Botte 1950; Zinn et al., 1993) Reactor production of .sup.67 Cu at lower specific activities using a thermal neutron flux according to the reaction .sup.63 Cu(n,.gamma.).sup.64 Cu has also been reported. (Hetherington et al., 1986). As such, .sup.64 Cu is currently available for the preparation of radioimaging and radiotherapeutic agents only in limited quantities and on a limited basis via the fast neutron reaction using a nuclear reactor. Hence, improved methods are needed for producing .sup.64 Cu and other radionuclides from solid target materials using readily available in-house accelerators.
The feasibility of using a hospital-sized proton cyclotron for producing a broad range of radionuclides, including .sup.64 Cu, has been investigated. (Nickles et al. 1991). Cylclotron production of .sup.64 Cu has been reported from pressed powder pellets of elemental .sup.64 Ni according to the reaction .sup.64 Ni(d,2n).sup.64 Cu (Zweit et al., 1991), and from a stack of enriched .sup.64 Ni plated foils according to the reaction .sup.64 Ni(p,n).sup.64 Cu (Szelecsenyi et al., 1993). Co-production of .sup.55 Co and .sup.64 Cu from a nickel foil soldered onto a copper or stainless steel support has also been reported. (Maziere et al., 1983). These approaches, while confirming the feasibility of producing .sup.64 Cu, did not produce clinically significant amounts of .sup.64 Cu and did not produce .sup.64 Cu at a specific activity which was suitable for use in clinical radiopharmaceutical diagnostic and/or therapeutic compositions. Moreover, these approaches did not address the practical difficulties encountered in scaling up to the high power irradiation required for such commercially useful production.
The use of a cyclotron accelerator for producing other radionuclides is reported in U.S. Pat. No. 4,487,738 to O'Brien et al. (.sup.67 Cu), Mirzadeh et al., 1986 (.sup.67 Cu), Piel et al., 1991 (.sup.62 Cu), Sharma et al., 1986 (.sup.55 Co), Mushtaq and Qaim, 1989 (.sup.73 Se), Michael et al., 1981 (123I), Guillaume et al., 1988 (.sup.38 K), Vaalburg et al., 1985 (.sup.75 Br), Rosch and Qaim, 1993 (.sup.94m Tc) and Ferrier et al., 1983 (.sup.13 N from solid .sup.13 C). While these references disclose various reactions, targets, target holders, conveyance systems and separation systems, the references do not provide a comprehensive system or method for the automated, in-house production of radionuclides from solid targets in significant yields and at specific activities suitable for diagnostic or therapeutic use.